tbuckley/cabot-search huggingface dataset:
18F-FDG PET/CT Imaging of Idiopathic Granulomatous Mastitis
Authors: Keerthini Muthuswamy, Manil Subesinghe
Journal: Clinical Nuclear Medicine (2023)

Abstract A 43-year-old woman, who presented with a suspected left breast abscess, underwent serial ultrasounds, which demonstrated inflammatory changes that were nonresponsive to antibiotics and which spread to the contralateral breast. 18 F-FDG PET/CT demonstrated diffuse heterogeneous intense FDG uptake in both breasts with reactive axillary nodes. Breast biopsy confirmed granulomatous inflammation, and overall findings were consistent with idiopathic granulomatous mastitis. In the absence of histological analysis, idiopathic granulomatous mastitis is an important differential diagnosis to consider for bilateral abnormal breast uptake, and early recognition can facilitate prompt commencement of treatment.
Automated and miniaturized screening of antibiotic combinations via robotic-printed combinatorial droplet platform
Authors: Fangchi Shao, Hui Li, Kuangwen Hsieh, Pengfei Zhang, Sixuan Li, Tza-Huei Wang
Journal: Acta Pharmaceutica Sinica B (2023)

Antimicrobial resistance (AMR) has become a global health crisis in need of novel solutions. To this end, antibiotic combination therapies, which combine multiple antibiotics for treatment, have attracted significant attention as a potential approach for combating AMR. To facilitate advances in antibiotic combination therapies, most notably in investigating antibiotic interactions and identifying synergistic antibiotic combinations however, there remains a need for automated high-throughput platforms that can create and examine antibiotic combinations on-demand, at scale, and with minimal reagent consumption. To address these challenges, we have developed a Robotic-Printed Combinatorial Droplet (RoboDrop) platform by integrating a programmable droplet microfluidic device that generates antibiotic combinations in nanoliter droplets in automation, a robotic arm that arranges the droplets in an array, and a camera that images the array of thousands of droplets in parallel. We further implement a resazurin-based bacterial viability assay to accelerate our antibiotic combination testing. As a demonstration, we use RoboDrop to corroborate two pairs of antibiotics with known interactions and subsequently identify a new synergistic combination of cefsulodin, penicillin, and oxacillin against a model E. coli strain. We therefore envision RoboDrop becoming a useful tool to efficiently identify new synergistic antibiotic combinations toward combating AMR.
Chronic Liver Disease and Cirrhosis Mortality Rates Are Disproportionately Increasing in Younger Women in the United States Between 2000-2020
Authors: Yazan Abboud, Anna G. Mathew, Mohamad Aghaie Meybodi, Esli Medina-Morales, Saqr Alsakarneh, Catherine Choi, Yi Jiang, Nikolaos T. Pyrsopoulos
Journal: Clinical Gastroenterology and Hepatology (2023)
68Ga-PSMA Uptake in Solar Elastosis
Authors: Merve Nida Calderon Tobar, Hasan Önner, Cahit Yavuz
Journal: Clinical Nuclear Medicine (2023)

Abstract 68 Ga–prostate specific membrane antigen (PSMA) PET/CT scan for staging revealed increased 68 Ga-PSMA uptake in solar elastosis in a patient with prostate cancer. Solar elastosis is a degenerative condition of elastic tissue in the dermis caused by prolonged sun exposure. A few studies have demonstrated 68 Ga-PSMA uptake in cutaneous lesions. This case illustrates another instance of a benign cutaneous lesion accompanied by increased 68 Ga-PSMA uptake.
Myocardial, Retro-orbital, and Bilateral Testicular Metastases of an Ileal Neuroendocrine Tumor in 68Ga-DOTATATE PET/CT
Authors: Antoine Rogeau, Zoltan Kaplar, Francesco Fraioli
Journal: Clinical Nuclear Medicine (2023)

Abstract A 71-year-old man with a newly discovered metastatic grade II neuroendocrine tumor of the terminal ileum was referred for a 68 Ga-DOTATATE PET/CT scan to stage the disease and assess suitability for PRRT (peptide receptor radionuclide therapy). The patient was known to have secondary nodal and bone/liver metastatic disease through prior morphological investigations. PET images revealed an atypical pattern of metastatic disease, showcasing secondary lesions in bilateral extraocular muscles, the myocardium, and both testes. The patient was pauci-symptomatic and only reported fatigue and diarrhea. Management involved lanreotide administration, and PRRT is being envisaged.
Microglia out of place—mapping macrophages across the developing human body
Authors: Roman Sankowski, Marco Prinz
Journal: Cellular and Molecular Immunology (2023)

Macrophages (MΦs) are versatile cells found in every organ.Throughout the body, they work tirelessly to maintain tissues.To this end, they are instructed by their respective niches to express organ-specific genes and proteins, resulting in a variety of cell morphologies and highly specialized functions across different tissues [1].A recent study by Wang et al. used single-cell RNA sequencing to comprehensively profile human MΦ phenotypes across 19 organs between postconception weeks (PCW) 4 and 26 [2].This study revealed a surprising diversity of these cells and suggests new avenues of research.Postnatal MΦs exhibit various morphological and transcriptional phenotypes, ranging from highly branched forms (microglia in the brain and Langerhans cells in the epidermis) to bipolar shapes (perivascular and leptomeningeal MΦs) and even large multinucleated cells (bone osteoclasts) [3, 4].At all these sites, MΦs constantly survey their surroundings to recognize and remove cell debris, metabolites, and invading pathogens and even regulate blood flow [4, 5].Reflecting their diverse roles, MΦs express various marker proteins, including general pan-MΦ markers, such as F4/80 and CD11b, and more specialized proteins, such as Mrc1 and Lyve1 in perivascular MΦs and Sall1 and Hexb in microglia in the central nervous system (CNS).Prior to the study by Wang et al., the prenatal landscape of MΦs across different tissues was not fully resolved.This new study broadens our understanding of human tissue MΦs by identifying microglia-like cells in the fetal epidermis, testicles, and heart.Furthermore, it highlights the presence of proangiogenic MΦs (termed PraMs) across various organs.Questions arise regarding the functions of these cells and their origins.Human fetal development is marked by extensive organ growth and refinement (Fig. 1A).This process involves cells from different lineages that colocalize, giving rise to parenchymal cells, blood and lymphatic vessels, and nerves, which later intricately interconnect within the adult organ.Wang et al. found that direct contact with neural crest cells induces microglia-like MΦ phenotypes in the human epidermis.Spatial distribution analysis indicates a preferential enrichment of these cells in the skin of the back and the head rather than the limbs or abdomen.This distribution pattern aligns with the pattern of neural crest cell (NCC) migration.Validation experiments confirmed a direct interaction of SOX10 + melanocyte precursor cells.Mechanistically, the authors demonstrated that the depletion of microglia-like cells
Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants
Authors: Karen Y. He, Ekaterina A. Khramtsova, Alfredo Cabrera-Socorro, Yanfei Zhang, Shuwei Li, Brice A. J. Sarver, Bart Smets, Qingqin S. Li, Louis De Muynck, Antonio R. Parrado, Simon Lovestone, Mary Helen Black
Journal: Molecular Neurodegeneration (2023)
Elevated 18F-AIF-FAPI-04 Uptake in Hepatic Hemangioma
Authors: Yuyun Sun, Xin Cai, Zheng Wang, Yun Sun, Jingyi Cheng
Journal: Clinical Nuclear Medicine (2023)

Abstract A 67-year-old woman who was diagnosed with intrahepatic cholangiocellular carcinoma (CCC) by biopsy underwent 18 F-FDG and 18 F-AIF-FAPI-04 PET/CT for initial and treatment assessment. In addition to CCC, she had a history of hepatic hemangioma for 3 years. 18 F-FDG PET/CT images showed increased uptake in CCC, but no uptake in hemangiomas. However, images on 18 F-AIF-FAPI-04 PET/CT indicated negative 18 F-AIF-FAPI-04 uptake in CCC, but intense activity in hemangiomas. Our case illustrates that hepatic hemangioma demonstrated intense 18 F-AIF-FAPI-04 uptake, and final diagnosis should be made with caution.
Does Serum Creatinine Reflect Muscle Mass in Patients with Kidney Failure?
Authors: Sankar D. Navaneethan, William E. Mitch
Journal: Journal of the American Society of Nephrology (2023)

1Section of Nephrology, Selzman Institute for Kidney Health, Baylor College of Medicine, Houston, Texas 2Section of Nephrology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas 3Michael E. DeBakey VA Medical Center Health Services Research & Development Center for Innovations in Quality, Effectiveness and Safety, Houston, Texas 4Institute of Clinical and Translational Research, Baylor College of Medicine, Houston, Texas Correspondence: Dr. William E. Mitch, Section of Nephrology, Baylor College of Medicine, One Baylor Plaza, 100.37S, Houston, TX 77030. Email: [email protected] Published online ahead of print. Publication date available at www.jasn.org. See related article, "Muscle Mass and Serum Creatinine Concentration by Race and Ethnicity among Hemodialysis Patients," on pages 66–73.
Bariatric Surgery in Women with Polycystic Ovary Syndrome
Authors: Suhaniya N.S. Samarasinghe, Casper Woods, Alexander Dimitri Miras
Journal: Metabolism (2023)

Polycystic ovary syndrome (PCOS) is the most common endocrine condition in premenopausal women and is a common cause of anovulatory subfertility. Although obesity does not form part of the diagnostic criteria, it affects a significant proportion of women with PCOS and is strongly implicated in the pathophysiology of the disease. Both PCOS and obesity are known to impact fertility in women; obesity also reduces the success of assisted reproductive technology (ART). With or without pharmacotherapy, lifestyle intervention remains the first-line treatment in women with PCOS and obesity. Bariatric surgery is still an experimental treatment in women with PCOS and subfertility. This review will present an overview of the pathophysiology of PCOS and obesity and the role of bariatric surgery. Although data are sparse regarding the impact of bariatric surgery on subfertility in women with PCOS and obesity, existing studies point to a beneficial role in treating metabolic and reproductive dysfunction.
Antibiotic use and outcome in patients with negative blood cultures, a new target population for antimicrobial stewardship interventions: A prospective multicentre cohort (NO-BACT)
Authors: José Antonio Girón-Ortega, Raquel Fernández-Guerrero, Montserrat Montes de Oca Arjona, Fátima Galán-Sanchez, Galadriel Pellejero Sagastizábal, Elena Morte Romea, Marina de Cueto, Margarita Beltrán Garcia, Zaira Palacios-Baena, Silvia Jiménez Jorge, Jesús Rodríguez-Baño, Pilar Retamar-Gentil
Journal: Journal of Infection (2023)

Objectives To evaluate the appropriateness of antimicrobial treatment and the risk factors for mortality in patients with negative blood cultures (BC), in order to evaluate whether this population would be a suitable target for antimicrobial stewardship (AMS) interventions. Methods A multicentre prospective cohort study of patients with negative BC in three Spanish hospitals between October 2018 and July 2019 was performed. The main endpoints were appropriateness of antimicrobial treatment (evaluated by two investigators according to local guidelines) and 30-day mortality. Cox-regression was performed to estimate the association between variables and 30-day mortality. Results Of 1011 patients in whom BC were obtained, these were negative in 803 (79%) and were included; 30-day mortality was 9% (70 patients); antibiotic treatment was considered inappropriate in 299 (40%) of 747 patients evaluated at day 2, and in 266 (46%) of 573 at day 5-7. The variables independently associated with increased risk of 30-day mortality were higher age (HR 1.05; 95% CI 1.03-1.07), neoplasia (HR 2.73; 95% CI 1.64-4.56), antibiotic treatment in the 48 hours prior to BC extraction (HR 2.06; 95% CI 1.23-3.43) and insufficient antibiotic coverage at day 2 after BC obtainment (HR 2.35; 95% CI 1.39-4.00). Urinary, catheter and biliary sources of infection were associated with lower risk (HR 0.40; 95% CI 0.20-0.81). Conclusions Antimicrobial treatment is frequently inappropriate among patients with negative BC; insufficient antibiotic coverage at day 2 was associated with mortality. These results suggest that patients with negative BC are a suitable population for AS interventions. Summary Antimicrobial treatment in patients with negative blood culture was frequently inappropriate, and inappropriate coverage at day 2 was associated with increased risk of death. These data support the consideration of this population as a potential target for antimicrobial stewardship interventions.
RAB7 deficiency impairs pulmonary artery endothelial function and promotes pulmonary hypertension
Authors: Bryce Piper, Srimathi Bogamuwa, Tanvir Hossain, Daniela Farkas, Lorena Rosas, Adam C. Green, Geoffrey Newcomb, Nuo Sun, Jose A. Ovando-Ricardez, Jeffrey C. Horowitz, Aneel R. Bhagwani, Hu Yang, Tatiana V. Kudryashova, Mauricio Rojas, Ana L. Mora, Pearlly Yan, Rama K. Mallampalli, Elena A. Goncharova, David M. Eckmann, Laszlo Farkas
Journal: Journal of Clinical Investigation (2023)

Pulmonary arterial hypertension (PAH) is a devastating and progressive disease with limited treatment options. Endothelial dysfunction plays a central role in the development and progression of PAH, yet the underlying mechanisms are incompletely understood. The endosome-lysosome system is important to maintain cellular health, and the small GTPase RAB7 regulates many functions of this system. Here, we explored the role of RAB7 in endothelial cell (EC) function and lung vascular homeostasis. We found reduced expression of RAB7 in ECs from patients with PAH. Endothelial haploinsufficiency of RAB7 caused spontaneous pulmonary hypertension (PH) in mice. Silencing of RAB7 in ECs induced broad changes in gene expression revealed via RNA-Seq, and RAB7-silenced ECs showed impaired angiogenesis and expansion of a senescent cell fraction, combined with impaired endolysosomal trafficking and degradation, suggesting inhibition of autophagy at the predegradation level. Furthermore, mitochondrial membrane potential and oxidative phosphorylation were decreased, and glycolysis was enhanced. Treatment with the RAB7 activator ML-098 reduced established PH in rats with chronic hypoxia/SU5416. In conclusion, we demonstrate for the first time to our knowledge the fundamental impairment of EC function by loss of RAB7, causing PH, and show RAB7 activation to be a potential therapeutic strategy in a preclinical model of PH.
Advances in the Management of Classical Hodgkin Lymphoma
Authors: Ryan C. Lynch
Journal: Journal of the National Comprehensive Cancer Network (2023)

The development of brentuximab vedotin, nivolumab, and pembrolizumab has revolutionized the treatment of classical Hodgkin lymphoma. Continuous efforts are underway to improve the established early-line treatment regimens, incorporating these novel systemic therapies as either replacements for or additions to conventional agents. Although brentuximab vedotin, nivolumab, and pembrolizumab have demonstrated efficacy both as monotherapies and in combinations, critical questions remain regarding the sequencing of these agents, as well as the role of radiation therapy and interim PET scans.
The NCCN 2023 Annual Congress: Hematologic Malignancies
Authors: Crystal S. Denlinger
Journal: Journal of the National Comprehensive Cancer Network (2023)

T he treatment of hematologic malignancies is increasingly complex as a result of the rapid pace and numerous advances in knowledge of their biologies and treatments.In mid-September, NCCN held the 2023 Annual Congress: Hematologic Malignancies, a 2-day hybrid symposium that addressed the latest in therapeutic advances, updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines), and treatment debates across the broad spectrum of blood cancers.Returning to San Francisco for the first time since 2019, the meeting featured insights from world-renowned experts on providing optimal, evidence-based treatment for various blood cancers, plus best practices for protecting vulnerable populations in a changing health care landscape.Chaired by
Updates in the Management of Myelofibrosis
Authors: Andrew T. Kuykendall
Journal: Journal of the National Comprehensive Cancer Network (2023)

The JAK inhibitors ruxolitinib, fedratinib, and pacritinib have demonstrated significant activity in improving symptoms and spleen size, as well as quality of life, in patients with myelofibrosis. Additionally, the recent approval of another JAK inhibitor, momelotinib, for patients with myelofibrosis and anemia has further expanded the available treatment options for this malignancy. As research continues to reveal the best treatment strategies, clinical trials will remain an essential avenue for improving outcomes in this patient population.
Navigating the Challenges: Effective Management of Toxicities in CAR T-Cell Therapies
Authors: Olalekan O. Oluwole, Salyka Sengsayadeth
Journal: Journal of the National Comprehensive Cancer Network (2023)

CAR T-cell therapy has dramatically changed the treatment landscape of many hematologic cancers, but it carries some risk. Cytokine-release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome can be life-threatening acute toxicities that require prompt identification, severity grading, and intervention. Appropriate use of tocilizumab and steroids may mitigate the side effects of CRS. Some of the chronic toxicities, such as cytopenias and hypogammaglobulinemia, should be differentiated from other possible causes; they also may respond to well-informed management.
Management of Toxicities of BTK Inhibitors in B-Cell Malignancies
Authors: Muhammad Saad Hamid, Kirollos S. Hanna
Journal: Journal of the National Comprehensive Cancer Network (2023)

Brüton’s tyrosine kinase (BTK) inhibitors have significantly advanced treatment options for patients with B-cell malignancies; however, side effects with these agents are not uncommon, and a multidisciplinary approach is necessary for monitoring and managing adverse events such as bleeding, hypertension, and atrial fibrillation. In the treatment of patients on BTK inhibitors, maintaining communication between patients and all providers is essential, particularly concerning the use of any concurrent medications or supplements, as is educating patients on identifying early risk factors and reporting any signs or symptoms of toxicities. Ongoing clinical studies with both covalent and noncovalent BTK inhibitors are expected to further increase the understanding of these toxicities while improving the efficacy and safety of this class of medications.
Incorporating Immunotherapeutic Strategies in the Management of Relapsed/Refractory Multiple Myeloma
Authors: Shaji K. Kumar
Journal: Journal of the National Comprehensive Cancer Network (2023)

The emergence of immunotherapy has changed the treatment strategy for multiple myeloma, both in the early disease setting and in relapsed/refractory disease. Although daratumumab has been routinely incorporated into various combination regimens, T-cell–redirecting approaches, such as bispecific T-cell engagers and CAR T-cell therapy, are emerging. In patients with highly refractory disease, these approaches have robustly impacted both progression-free and overall survival. Most of these agents target the B-cell maturation antigen. Drugs with new targets are also in development, which will further extend the value of immunotherapeutic strategies in myeloma.
Chronic Myeloid Leukemia/Myelofibrosis: TKI Therapy and Toxicity Management
Authors: Gabriela S. Hobbs, Christopher Bell
Journal: Journal of the National Comprehensive Cancer Network (2023)

Recent advances in the understanding of the molecular basis of chronic myeloid leukemia (CML) and myelofibrosis have led to more effective treatment options, with survival now close to that of age-matched controls in CML. The latest updates to the NCCN Guidelines for CML reflect the rapidly evolving treatment landscape, emphasizing the increasing importance of personalized medicine and various targeted therapies. For patients with CML, standard of care involves tyrosine kinase inhibitors such as imatinib, dasatinib, bosutinib, nilotinib, ponatinib, and asciminib, tailored to patient-specific factors and the severity of adverse events. In patients with myelofibrosis, the Janus kinase inhibitors ruxolitinib, pacritinib, and fedratinib have yielded improved outcomes. Critical strategies for managing treatment-related adverse events to optimize the quality of life for patients with these hematologic malignancies were also highlighted.
Relapsed/Refractory CLL/SLL: Overcoming Resistance to Covalent BTKi and/or BCL2 Inhibitors
Authors: Brian T. Hill
Journal: Journal of the National Comprehensive Cancer Network (2023)

We are now in the era of targeted therapy for frontline chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), with current treatments demonstrating favorable long-term outcomes. However, patients with double-refractory CLL whose disease has relapsed or been refractory to treatment with both a BTK and BCL-2 inhibitor present a unique challenge; although the number of patients experiencing relapse after first-line chemoimmunotherapy is likely to decrease, the number of those with double-refractory CLL is expected to increase. Various treatment strategies have been explored and noncovalent Bruton’s tyrosine kinase inhibitors, such as pirtobrutinib, show activity in the double-refractory CLL population. Further research and prospective trials are needed to refine these approaches and improve outcomes for patients with relapsed/refractory CLL/SLL.
Adult Acute Lymphocytic Leukemia: Strategies for Selection of Consolidation Therapy
Authors: Aaron C. Logan
Journal: Journal of the National Comprehensive Cancer Network (2023)

The 2 primary treatment options for adult acute lymphoblastic leukemia (ALL) are pediatric-inspired Berlin-Frankfurt-Münster protocols and the hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) regimen—these treatment strategies are now being augmented with novel agents. Current strategies also emphasize measurable residual disease (MRD) quantification as a critical tool for determining the treatment course. For patients with MRD-positive ALL, the standard of care has shifted toward blinatumomab, resulting in improved outcomes and survival rates. Another novel agent, inotuzumab ozogamicin, is also being explored for the treatment of earlier stages of disease in patients with ALL. For Philadelphia chromosome (Ph)–negative ALL, the NCCN Guidelines recommend treatment with blinatumomab followed by allogeneic transplants for patients remaining MRD-positive after initial therapy. For patients achieving MRD negativity at the level of 10 -4 , blinatumomab is now recommended as consolidation, with or without subsequent allotransplant, depending on patient disease risk features. For Ph-positive ALL, the use of tyrosine kinase inhibitors in combination with blinatumomab has demonstrated excellent efficacy, indicating the growing importance of combination targeted therapies to improve outcomes and decrease the toxicity of therapy in adults with ALL.